Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE1V1OW)

• DOT Name: Synaptotagmin-14 (SYT14)
• Synonyms: Synaptotagmin XIV; SytXIV
• Gene Name: SYT14
• Related Disease:
  Dental caries
  Glioma
  Isolated cleft lip
  Multiple sclerosis
  Autosomal recessive spinocerebellar ataxia 11
• UniProt ID: SYT14_HUMAN
• Pfam ID: PF00168
• Sequence:
  MAIEGGERTCGVHELICIRKVSPEAVGFLSAVGVFIILMLLLFLYINKKFCFENVGGFPD
  LGSEYSTRKNSQDKIYNSYMDKDEHGSSSESEDEALGKYHEALSRTHNSRLPLADSRQRN
  YAWETRQKYSPLSAEYDGYSSEASIDEGNCIQRMRRTPPLDELQPPPYQDDSGSPHLSCT
  PSEIGDSKCEFSHCSNSPRCSYNKCPSEGSTGHEIESFHNKGYEEDVPSDSTAVLSPEDM
  SAQGSSSQLPKPFDPEPEAKYGTLDVTFDYDSQEQKLLVTVTAVTDIPTYNRTGGNSWQV
  HLVLLPIKKQRAKTSIQRGPCPVFTETFKFNHVESEMIGNYAVRFRLYGVHRMKKEKIVG
  EKIFYLTKLNLQGKMSLPVILEPSYNHSGCDSQMSVSEMSCSESTSSCQSLEHGSVPEIL
  IGLLYNATTGRLSAEVIKGSHFKNLAANRPPNTYVKLTLLNSMGQEMSKCKTSIRRGQPN
  PVYKETFVFQVALFQLSDVTLILSVYNKRSMKRKEMIGWISLGLNSSGEEELNHWTEMKE
  SKGQQVCRWHALLES
• Function: May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent.
• Tissue Specificity: Highly expressed in fetal and adult brain tissue.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dental caries	DISRBCMD	Strong	Genetic Variation	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[4]
Autosomal recessive spinocerebellar ataxia 11	DISK0GCG	Supportive	Autosomal recessive	[5]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Synaptotagmin-14 (SYT14).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synaptotagmin-14 (SYT14).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Synaptotagmin-14 (SYT14).	[9]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Synaptotagmin-14 (SYT14).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synaptotagmin-14 (SYT14).	[10]

References

• [1] Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nat Commun. 2019 Jun 24;10(1):2773. doi: 10.1038/s41467-019-10630-1.
• [2] RNAi-mediated SYT14 knockdown inhibits the growth of human glioma cell line U87MG.Brain Res Bull. 2018 Jun;140:60-64. doi: 10.1016/j.brainresbull.2018.04.002. Epub 2018 Apr 7.
• [3] Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci.Nat Genet. 2012 Sep;44(9):968-71. doi: 10.1038/ng.2360. Epub 2012 Aug 5.
• [4] Common variation near IRF6 is associated with IFN--induced liver injury in multiple sclerosis.Nat Genet. 2018 Aug;50(8):1081-1085. doi: 10.1038/s41588-018-0168-y. Epub 2018 Jul 16.
• [5] Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation. Am J Hum Genet. 2011 Aug 12;89(2):320-7. doi: 10.1016/j.ajhg.2011.07.012.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.